Recently, tumor cells have been found to selectively accumulate certain n-3 fatty acids such as cis-4,7,10,13,16,19-docosahexenoic acid (DHA). DHA-paclitaxel, a conjugate of DHA and paclitaxel, has a greatly increased therapeutic efficacy and reduced side effects in both experimental animals and patients compared to free paclitaxel. We have synthesized a proprietary DHA-camptothecin conjugate that showed remarkable antitumor activity in experimental animals. We have filed a provisional patent application covering this invention (US 60/401,195). The objectives of this proposal are to synthesize novel DHA camptothecin conjugates, evaluate their antitumor activity in vitro and in experimental animals. It is expected that the novel DHA conjugates will have increased antitumor efficacies and reduced toxic side effects.
